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THE EFFECT OF MINOCYCLINE ON NEUROINFLAMMATION AFTER BRAIN TRAUMA
  1. Gregory Scott1,
  2. Amy Jolly1,
  3. Peter O Jenkins1,
  4. Anne Lingford-Hughes1,
  5. Maneesh Patel2,
  6. Anthony Goldstone1,
  7. Paul Matthews1,
  8. David Sharp1
  1. 1 Division of Brain Sciences, Imperial College London
  2. 2 Imperial College Healthcare NHS Trust

Abstract

Background Traumatic brain injury (TBI) triggers potentially harmful chronic neuroinflammation. The antibiotic minocycline is neuroprotective in animal models of TBI through the inhibition of microglial activation. We used [11C]PBR28 positron emission tomography (PET) to test whether minocycline reduces microglial activation after TBI.

Methods Fifteen patients 6 months-11 years after a moderate-severe TBI and age-matched controls had MRI, neuropsychological testing and PET. Patients received either minocycline 100 mg orally twice daily or no drug (2:1 ratio) for 12 weeks, and were followed up at 12 weeks and 6 months.

Results In patients, [11C]PBR28 binding was increased in white matter (WM) and thalamus. Patients had MRI evidence of WM damage at baseline and also had longitudinal volume loss (mean, −1.6%/year). WM damage and atrophy were highest in areas of increased [11C]PBR28 binding. [11C]PBR28 binding after 12 weeks' minocycline was significantly reduced (e.g. mean WM volume of distribution change=−23.3%, 95% CI −40.9 to −5.6%), indicating a reduction in microglial activation.

Conclusion Progressive volume loss in white matter with high microglial activation indicates on-going neurodegeneration. Minocycline reduced [11C]PBR28 binding, suggesting a treatment effect on microglial activation. These findings support the case for further clinical evaluation of minocycline as a treatment for neurodegeneration after TBI.

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